Study Stopped
Futility
Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)
Phase 3 Study of Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)
3 other identifiers
interventional
1,331
2 countries
12
Brief Summary
The purpose of this study is to determine if hypertonic saline with and without dextran can improve neurologic outcomes in victims of severe traumatic brain injury (TBI). Injury and lost blood from trauma can cause your body to go into shock (low blood pressure related to blood loss). This decreased blood flow can lead to organ damage. In order to restore the blood pressure and blood flow, the medics give fluids into the patients' veins as soon as possible. This is called "resuscitation". The fluid most commonly used is "isotonic" or one that is the same salt concentration as the blood. The investigators are trying to determine if infusing a "hypertonic" fluid or one more concentrated than the blood can increase the blood pressure and restore blood flow more efficiently. The hypertonic fluids they are using are called hypertonic saline with dextran (HSD) and hypertonic saline (no dextran). Hypertonic saline is a salt solution that is slightly more concentrated than blood. Dextran is a sugar solution.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2006
Typical duration for phase_3
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 17, 2006
CompletedFirst Posted
Study publicly available on registry
April 19, 2006
CompletedStudy Start
First participant enrolled
May 1, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2010
CompletedResults Posted
Study results publicly available
May 9, 2011
CompletedMay 19, 2011
May 1, 2011
3 years
April 17, 2006
February 11, 2011
May 16, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Completer Analysis
Glasgow outcome score extended (GOSE) contains eight categories: 1. Dead, 2. Vegetative State (VS), 3. Lower Severe Disability (Lower SD), 4. Upper Severe Disability (Upper SD), 5. Lower Moderate Disability (Lower MD), 6. Upper Moderate Disability (Upper MD), 7. Lower Good Recovery (Lower GR) and 8. Upper Good Recovery (Upper GR). A measured neurological outcome of GOSE≤4 is a poor outcome of severe disability, vegetative state, or death. Completer analysis includes only those patients with GOSE completed at 6 months after injury.
6 months after injury
Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis
Glasgow outcome score extended (GOSE) contains 8 categories: 1. Dead, 2. Vegetative State, 3. Lower Severe Disability, 4. Upper Severe Disability, 5. Lower Moderate Disability, 6. Upper Moderate Disability, 7. Lower Good Recovery and 8. Upper Good Recovery. To adjust for 15% of subjects with absent 6-month GOSE data, an analysis using 20 hot deck imputations for the 6-month GOSE was done using data from patients who were discharged alive based on 1-month post discharge GOSE data or discharge GOSE (if 1-month post discharge data were not available), length of hospital stay, and treatment group.
6 months after injury
Secondary Outcomes (14)
Subgroup of Participants With Head Abbreviated Injury Scores (AIS) Greater Than or Equal to 4 (Head AIS≥4) Assessed to Have Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis
6 months after injury
Subgroup of Participants With Head Abbreviated Injury Scores (AIS) Greater Than or Equal to 2 (Head AIS≥2) Assessed to Have Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis
6 months after injury
Disability Rating Score (DRS) Categories of Disability
6 months after injury
28 Day Survival
28 days after injury
Survival at Hospital Discharge up to 6 Months From Date of Injury
Date of hospital discharge up to 6 months from date of injury
- +9 more secondary outcomes
Study Arms (3)
7.5% hypertonic saline/6% dextran (HSD)
EXPERIMENTAL250 ml intravenous bolus administration of 7.5% saline/6% dextran 70
7.5% hypertonic saline (HS)
EXPERIMENTAL250 ml intravenous bolus administration of 7.5% hypertonic saline
0.9% normal saline (NS)
PLACEBO COMPARATOR250 ml intravenous bolus administration of 0.9% saline
Interventions
250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
250 ml intravenous bolus administration of 7.5% hypertonic saline administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
250 ml intravenous bolus administration of 0.9% saline administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Eligibility Criteria
You may qualify if:
- Blunt trauma
- Pre-hospital Glasgow Coma Scale equal to or less than 8(GCS≤8)\*
- Age 15 years or older or 50 kg or more
You may not qualify if:
- Known or suspected pregnancy
- Age younger than 15 years or less than 50 kg if age unknown
- Ongoing pre-hospital cardiopulmonary resuscitation (CPR)
- Administration of more than 2L crystalloid or any colloid or blood products
- Severe hypothermia (T less than 28C)
- Drowning or asphyxia due to hanging
- Burns TBSA more than 20%
- Isolated penetrating injury to the head
- Inability to obtain pre-hospital intravenous access
- Time of call received at dispatch to study intervention more than four hours
- Known prisoners
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Washingtonlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Institute of Neurological Disorders and Stroke (NINDS)collaborator
- U.S. Army Medical Research and Development Commandcollaborator
- Canadian Institutes of Health Research (CIHR)collaborator
- Canadian Department of National Defencecollaborator
- Heart and Stroke Foundation of Canadacollaborator
Study Sites (12)
Alabama Resuscitation Center, University of Alabama
Birmingham, Alabama, 35249, United States
Orange County/UC Irvine
Orange, California, 92868, United States
UCSD-San Diego Resuscitation Research Center
San Diego, California, 92103, United States
Iowa Resuscitation Network, University of Iowa Carver College of Medicine
Iowa City, Iowa, 52242, United States
Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University
Portland, Oregon, 97239, United States
The Pittsburgh Resuscitation Network, University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
The Regional Medical Center at Memphis
Memphis, Tennessee, 38103, United States
Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Seattle-King County Center for Resuscitation Research, University of Washington
Seattle, Washington, 98195, United States
Milwaukee Resuscitation Network, Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research Institute
Ottawa, Ontario, K1Y4E9, Canada
Toronto Regional Resuscitation Research Out-of-Hospital Network, University of Toronto
Toronto, Ontario, M5B1W8, Canada
Related Publications (2)
Bulger EM, May S, Brasel KJ, Schreiber M, Kerby JD, Tisherman SA, Newgard C, Slutsky A, Coimbra R, Emerson S, Minei JP, Bardarson B, Kudenchuk P, Baker A, Christenson J, Idris A, Davis D, Fabian TC, Aufderheide TP, Callaway C, Williams C, Banek J, Vaillancourt C, van Heest R, Sopko G, Hata JS, Hoyt DB; ROC Investigators. Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: a randomized controlled trial. JAMA. 2010 Oct 6;304(13):1455-64. doi: 10.1001/jama.2010.1405.
PMID: 20924011RESULTTisherman SA, Schmicker RH, Brasel KJ, Bulger EM, Kerby JD, Minei JP, Powell JL, Reiff DA, Rizoli SB, Schreiber MA. Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the Resuscitation Outcomes Consortium. Ann Surg. 2015 Mar;261(3):586-90. doi: 10.1097/SLA.0000000000000837.
PMID: 25072443DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The trial was stopped early for futility at a planned data and safety monitoring board review. The futility boundary was crossed for each of the 2 group comparisons (hypertonic saline/dextran vs normal saline and hypertonic saline vs normal saline).
Results Point of Contact
- Title
- Susanne May, PhD
- Organization
- Clinical Trial Center, University of Washington, Seattle, WA
Study Officials
- STUDY CHAIR
Myron L Weisfeldt, MD
Resuscitation Outcomes Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
April 17, 2006
First Posted
April 19, 2006
Study Start
May 1, 2006
Primary Completion
May 1, 2009
Study Completion
January 1, 2010
Last Updated
May 19, 2011
Results First Posted
May 9, 2011
Record last verified: 2011-05